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1. RESUMEN ESTRUCTURADO

1.2. Resumen en inglés

Background

Asthma is one of the most frequent chronic diseases of childhood. Despite the many advances in the knowledge of its pathophysiology and its treatment, even today it is accompanied by a very significant morbidity and mortality and represents a very important problem in terms of quality of life and care costs. It is important to provide evidence that helps to manage the disease in an efficient way, that is, trying to achieve the highest level of health from a given resources.

Objectives

To provide evidence that helps manage acute and chronic pediatric asthma in a more efficient way, through cost-effectiveness studies of the use of medications used to manage asthma exacerbations and/or their route of administration of these medications, and a study that identifies predictors of response to asthma controller medications to perform specific recommendations for a personalized and more efficient management of pediatric patients with persistent asthma.

Methods

Two economic evaluations were carried out, specifically cost-effectiveness studies to compare the administration of salbutamol via nebulization with compressed air and/or oxygen vs. by metered dose inhaler coupled to a spacer (IDM+S), and to compare the administration of prednisolone vs. oral dexamethasone for treatment of pediatric patients with asthma exacerbations. Additionally, a systematic literature

review of all studies identifying phenotypic or genotypic characteristics useful to predict the response to controller asthma medications.

Results

The cost-effectiveness study of NEB vs. IDM+S showed that for the treatment of asthma exacerbations in pediatric patients, the administration of salbutamol via IDM+S compared to its administration via NEB was associated with lower treatment costs (US$96.68 vs US$121.41 average cost per patient) and a higher probability of hospitalization avoided (0.9219 vs 0.8900), thus being considered the dominant strategy.

The cost-effectiveness study of prednisolone vs. oral dexamethasone showed that, compared to dexamethasone, prednisolone administration was associated with lower treatment costs (US$93.97 vs US$104.91 average cost per patient) and a similar probability of avoided hospitalization (0.9109 vs 0.9108). Because the cost-effectiveness analysis showed similar cost-effectiveness data in the two interventions analyzed, it was considered to use a cost-minimization analysis, thus choosing the least expensive option.

The systematic review of literature to identify studies that report phenotypic or genotypic characteristics useful to predict the response to controlling drugs in pediatric asthma, allowed to identify the following predictors: for preschool patients:

patients with allergic sensitization to at least one aeroallergen and/or peripheral blood eosinophils ≥300uL, with FECR2, or CRHR1 polymorphism are more likely to present a favorable response to daily therapy with ICS; non-atopic patients or with polymorphism 5/5 ALOX5 are more likely to respond favorably to antileukotriene

therapy. Finally, non-atopic patients are also more likely to respond favorably to intermittent therapy with ICS. For school and/or adolescent patients: patients with FeNO˃ 25ppb) levels, with an absolute number of peripheral blood eosinophils (350cells/mm3), with IgE˃200kU/L levels, with ECP˃15mcg/L levels, PC20 values in the methacholine challenge test<1mg/ml, and a VEF1/CVF value<80% are more likely to have a favorable response to therapy with ICS. On the other hand, patients with a shorter duration of the disease or those with an age less than 10 years, with a VEF1/CVF ratio value<80%, and with ULTE4˃100pg/mg levels, are more likely to have a favorable response to antileukotriene therapy.

For school and/or adolescent patients: black patients with atopic dermatitis, or children with at least one black grandparent, are more likely to have a favorable response to an increase in the dose of ICS that can range from two to five times the dose at which they presented inadequate symptom control. On the other hand, white patients (hispanic or non-hispanic) with atopic dermatitis, or with Gly/Arg ADRB2 polymorphism are more likely to present a favorable response with the addition of an antileukotriene when they present inadequate disease control with therapy established in phase 2 of treatment. Finally, non-hispanic white patients with atopic dermatitis, or without atopic dermatitis regardless of race, those with high reactance in oscillometry studies, or those with at least one black grandparent, are more likely to show a favorable response with the addition of an action bronchodilator (with the same or twice the dose of ICS) to therapy with which he was presenting inadequate control of asthma symptoms in step 2 of the management of the disease.

For school and/or adolescent patients: patients with FeNO˃25ppb, with a percentage of peripheral blood eosinophils≥2%, and BMI≥25, are more likely to have a favorable response to omalizumab treatment.

Conclusions

The studies presented in this paper show results that allow to manage pediatric asthma, both acute and chronic, in a more efficient way, that is, trying to achieve the highest level of health from given resources. The results of this work provide evidence that allow recommendations that can contribute not only to reduce the burden of asthma disease in the pediatric population and to improve the quality of life of affected patients and their entire family environment, but also to reduce the costs derived from asthma and its high burden, and their economic consequences of the disease, especially in low and middle - income countries such as Colombia.